Our bodies have complex regulatory mechanisms for food intake and energy expenditure, and the complexity continues to confound scientists seeking to understand these relationships. However, a little over 15 years ago, the discovery of a hormone called leptin, and a growing appreciation for its central role in managing both how much you eat and how much you move, has somewhat clarified the very muddy waters.
Why We Get Fat
Yes, we stole that from Gary Taubes. Taubes, among scores of science writers and actual scientists, has written extensively about the central role that the hormone insulin plays in the storage of body fat. It’s a well-established “fact of life” that insulin functions to let calories (i.e., energy, including carbohydrate and fat) into your cells for immediate usage, and/or storage for future usage. Limited amounts of carbohydrate can be stored in the liver and muscles in a form called glycogen, but it can be converted into an even more “compact” form for longer-term storage: fat.
See, body fat is not a bad thing. It’s what allows us as a species to survive long periods of food shortage. It’s what allows us to not eat for a couple days when we have the flu, and it’s what allows athletes to perform such amazing feats like running from New York to Los Angeles. But our bodies are pessimists. Our DNA always expects, despite the surplus of readily-available energy right now, that food will run out soon, and therefore, the only way to survive this coming famine is… store some energy as fat. It’s as natural as breathing.
But, of course, for those of us in the developed world, there is no famine. Ever. We’ve practically forgotten what it’s like to even be hungry, much less to be actually (temporarily) deprived of food. It almost seems like we (us Westerners) believe we have an inherent right to not be uncomfortable, feel pain, be hungry, or otherwise experience biology’s more unpleasant realities. “Rising above” the realities of nature is a dangerous – and foolhardy – trajectory. But we digress.
As fat is a storage depot for energy, it is important that your body have a way to measure how much fat you have at any given moment, and to control your behavior (primarily, eating and activity) accordingly.
Enter Leptin
Leptin is a fascinating, powerful hormone that was only discovered in 1994. As such, the research into leptin’s regulatory role is in its relative infancy. However, there are a few things that we do know:
- A primary function of leptin is to act as a messenger from stored fat to the brain to provide feedback about how much fat is in storage (i.e., the status of our “reservoir” of stored energy). Leptin is secreted into the bloodstream by fat cells (adipocytes) in proportion to the amount of fat mass. More fat, more leptin secreted.
- Leptin also acts as a satiety signal, blocking orexigenic hormones like NPY and AgRP that typically tell us to eat more (and move less). Higher levels of leptin (after meals) register in our brains to say that we’ve eaten enough – for now – and it’s okay to stop eating. Leptin also suppresses ghrelin, another “hunger hormone”. Getting the picture?
- Leptin is structurally and functionally similar to a family of chemical messengers called cytokines. These cytokines – including leptin – regulate important aspects of immunity and inflammation. Leptin can be considered one of the inflammatory (i.e. immune-stimulating) cytokines that fat cells secrete. More fat = more inflammatory cytokines secreted.
- Leptin registers in the brain at the arcuate nucleus of the hypothalamus, a central controller of both appetite and activity level. Key point: in order for leptin to deliver its message, it must register with the appropriate neurons in the hypothalamus. And that doesn’t always happen. [Storm clouds brewing.]
- Leptin, like insulin, is secreted after we eat, and elevated insulin levels cause the secretion of more leptin. Remember which macronutrient tends to drive insulin levels up the most? That’s correct: carbohydrate – particularly energy-dense, nutrient-poor carbohydrate sources like sugar, processed foods, grains and some dairy. Think a highly insulinogenic diet might contribute chronically elevated leptin levels? We do. Interestingly, in normal pancreatic cells, leptin tends to suppress insulin secretion. In the context of a high-carb diet, that could contribute to post-prandial (after eating) periods of prolonged elevated blood glucose. [More storm clouds.]
- Over-consuming food (even temporarily) will create an inflammatory state. This inflammation increases leptin secretion, leading to elevated levels of leptin in the blood (hyperleptinemia). Overeating quickly makes you leptin resistant. Of course, since (over)eating acutely triggers leptin secretion, grazing like an antelope will cause frequent rises in leptin levels. You are a not an antelope. And “all leptin, all the time” is not a good plan.
- Chronically increased leptin levels cause the hypothalamus to become desensitized to the leptin signal, creating leptin resistance, much like other cells can become insulin resistant in the presence of chronically high levels of insulin. Leptin resistance means that the satiety signal is not registering at the brain, which drives ongoing overconsumption of food, and reduces the amount of activity we are inspired to undertake. Furthermore, it turns you into a “sugar burner”, making it difficulty to access body fat for fuel. It also increases the proportion of fat intake that is stored as body fat. It’s like quicksand.
- There is a diurnal rhythm (daily cycle) to leptin secretion, and dysregulation of this pattern can create or exacerbate leptin resistance. (Translation: when you eat matters, too.) For those of you familiar with cortisol’s importance as a stress hormone, you might find this interesting: leptin’s rhythm has pretty much the opposite pattern from normal cortisol secretion, though leptin is tied to when you eat and cortisol is tied to the light/dark cycle. So their patterns are the same, but different.
- Smart people like Robb Wolf have long talked about how elevated cortisol levels will make weight loss incredibly difficult, and that is unequivocably true. However, we believe that the mechanism for this phenomenon is actually via leptin dysfunction. Elevated cortisol in the blood means more leptin is secreted (i.e. hyperleptinemia). More leptin secreted, over time, leads to pancreatic beta cell leptin resistance, so leptin no longer suppresses insulin secretion, leading to blood glucose volatility and likely insulin resistance. [The rain starts.] Worse yet, your hypothalamus becomes leptin resistant, no longer accurately registers how much body fat you have, and tells you to eat all the time, especially at night (since it thinks you’re not fat enough to survive). And… it doesn’t register properly even when you’ve eaten a large meal, so you overeat then, too. [Full-on hurricane.]
Now, this discussion has already stepped beyond what you really need to know about leptin, but many folks (ourselves included) really want to know the whys and hows. These points explain a few of those things – but there is so, so much more. Adiponectin, NPY, Agouti-related peptide, ghrelin, orexin, interleukin-6, TNF-α… the list is long. We’ve read literally hundreds of studies that have contributed to our understanding of this stuff, and will continue to learn as new research is published. We’re not going to throw down a comprehensive physiology lesson here (partly because we don’t know everything), but we wanted to share some of our thoughts on leptin as a kingpin of metabolic regulation.
Leptin – A Kingpin?
So, based on the thousands of leptin studies in the last decade-and-a-half, leptin seems to be a pretty central player in regulation of metabolism. (And don’t think that drug companies don’t want to figure out how to use leptin to treat obesity. They are scrambling to find a way. There’s big money in people being fat – and trying to get unfat.) But all that being said, why are we writing about leptin?
We Think It’s Important
We also think that there is no one “right” reason for why we get fat. Do highly-rewarding foods promote overconsumption? Unquestionably. Do foods that promote chronically elevated insulin levels tend to drive the deposition of body fat? Sure do. Do foods that promote increased gut permeability (and thus inflammation) play a role in leptin resistance and the pathogenesis of obesity? We think so.
But it’s not just food that makes you – or keeps you – fat. Sleep plays an important role, too. And chronic stress is a surefire way to create leptin resistance. (Cortisol potentiates leptin secretion, for those of you who care about the how.) Creating excessive inflammation via over-exercising (or, as we prefer, under-recovering) can further disturb leptin and insulin signaling.
There Is No Easy Button
We’re not the only people who view altered leptin signaling as a central problem in the pathogenesis of both obesity and other metabolic conditions, including thyroid dysfunction and some eating disorders. But as central as proper leptin function is, it is not the cure for all your woes. It will not be the “quick fix” to finally getting lean. We observe many trends in our online fitness/health community, and lots of people are writing about leptin these days. But please understand that this is only one aspect of the underlying mechanisms that make each of us healthy… or not as healthy as we could be. It’s not that easy. Sorry. (Yes, we’re #paleobuzzkills.)
In order to optimally integrate all these factors into a life that is healthier in the future than it was in the past, you have to address all the components. Unfortunately, simply eating a healthy Paleo-ish diet and exercising smarter-not-harder cannot undo all the damage that your old habits caused. The route from B to A is not always the same as it was from A to B.
So How Do I Get Fixed?
We’ll be writing more about this in upcoming posts, so stay tuned for implementation recommendations. In the meantime, take a good, hard look at your individual context from a big-picture perspective.
- Review our Health Equation post. Do some introspection.
- Read our Nutrition in 60 Seconds and implement the concepts.
- If you are still struggling with health issues or food cravings, give our Whole30 program a shot.
- Turn off the TV, the computer, and your iPhone. Staying connected is not always healthy.
- Get some good sleep tonight.
Your health depends on it.
In addition, you can also pick up the book Mastering Leptin. Byron Richards has been writing comprehensively about leptin since 2002, and many leptin protocols floating around the internet are based on his material.
As always, we welcome your questions, comments and general discussion.
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The concept of why we are overweight is one psychologists all over the world are working on.
There are many reasons for which we over eat and even more for why we don’t work out.
To make a change it takes a decision and it takes action, the problem most have though is that they are too hard on themselves when they fail.
You don’t need to be, change is difficult. For most people it takes 5-8 attempts before you can make a change permanent. So if you slip once, that is okay, learn from it and make sure not to make the same mistake again and move on.
What a fascinating article. Thank you for providing this to your readers!
I’m really excited for the rest of this series. A lot of the recommendations that we as Paleo practitioners make will take folks most of the way toward their goals of reversing insulin resistance and preventing adrenal fatigue, but leptin resistance may be that last little bit that many of us are looking for.
If any of you have that mindset of “I seem to be doing everything right but I’m just not losing those last few pounds”, spend some time learning about leptin resistance and ask lots of questions of us!
okay, so any advice to someone who knows that their cortisol levels are going to be high while i am in nursing school AND just started a job working at a hospital at night 2 nights a week? i have been paleo for over a year. meal timing? better foods?
just quitting the night job is not an option, either. (they are paying for school and have agreed to hire me after school, not to mention, there are precious few jobs for entry-level people in this economy.)
thanks for any help!
ck
Colleen,
Get as much sleep as you can. Don’t eat at night, even if you’re awake (drink tea or mineral water but no calories). Start your day with a big protein-rich meal. Try to maintain a “regular” meal schedule, preferably starting your day (in the morning) with a good meal and eating 2-3 other meals, ending several hours before bed. Don’t overexercise, or even do any high-intensity stuff at all (since you have a tiny margin for error on that). That’s general stuff, but it might help. And stay tuned to the 9 Blog for our “part 2” piece about our recommendations.
Dallas
So weird, the NYTimes addressed leptin today as well:
http://www.nytimes.com/2011/10/27/health/biological-changes-thwart-weight-loss-efforts-study-finds.html?kjnd=i7BLie0lFOiFh6vGOhUyJ6%2FcWZfgiYXP2BT5UCV99CM%3D-ebb9a494-79be-44c0-91b9-dd46e2d6027b_wIt5mRBjGAc%2FwuAv7lxK3QtisSyfbJV1RXGpzfxPCt00jRoy3KQfT2ecwUDnVgcw
Thank you SO much for this. You two always do such a graceful job of synthesizing all the info floating around out there and making it easier to understand. So grateful for you beautiful people!
Great post! This is so valuable in the understanding of how leptin works.
Thanks for a great post. One thing I’m confused about: In Robb’s book he talks about how protein releases the largest amount of PYY, fat is next, and finally carbohydrate. PYY is also supposed to increase leptin sensitivity. Leptin tells us we are full, another satiety hormone. So it seems contradictory to me that eating carbohydrate produces the last amount of PYY but the most amount of Leptin? So sorry if this was a wretchedly constructed question but thanks for all your help.
Meaghan,
Great question, and good on you for noting that apparent discrepancy. From my understanding, which is admittedly incomplete, the difference has to do with which stimulus provokes which response. PYY is more of a acute satiety hormone, whereas leptin is a somewhat more “chronic” monitor, and acts as a protective measure against harmful overconsumption (that would provoke adipocyte “overfilling” and inflammation). Since insulin tends to elevate leptin (but not the other way around), carbohydrates (and highly insulinogenic proteins like beef) will tend to promote more leptin secretion, but that is also initiated by consumption of large meals, especially high-carb, high-fat meals (which also can contribute to elevated insulin levels via inducing some degree of insulin resistance. So… carbohydrate doesn’t give us much satiety via PYY, but it significantly suppresses ghrelin and potentiates leptin secretion at higher levels, so indirectly, carbohydrate does give us some degree of satiety, but not as reliably, and not until higher levels of ingestion (which, of course, is inflammatory and provokes a significant insulin response). So the apparent contradiction is simply present because there are multiple, redundant and overlapping systems that function to regulate energy intake and expenditure. To be honest, I don’t feel like I know everything there is to know about this stuff, but I’m sharing the salient points since we think that this concept of central regulation of metabolism, immunity, and endocrine function is fascinating, critical stuff. I hope my ramblings above helped clarify the complexity a little. If not, let me know and I’ll try again. ;)
Best,
Dallas
Thanks, Dallas. No, you did a fine job. When it comes to our physiology and biology, it seems most everything is multifactorial, so I figured that all this stuff somehow stitches together a patchwork quilt of sense. And again, I’m new to this whole thing since about a few months ago, but admittedly, I have been quite a book/blog worm. I just get super stoked about the more sciency stuff. :)
Thank you so much, Dallas! i have noticed that i am starving at night. since i have been paleo for a while, i am rarely STARVING during the day, unless i didn’t get enough in my post workout meal. i really appreciate the advice!
ck
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Excellent article! This fuels my “need to know more” and presents it in a way that’s well, easily digestible (no pun intended). Looking forward to part two and beyond!
Dallas or Melissa – are you continuing on this post? I’m curious if you’ve ever had any clients that experienced ravenous hunger between about 4-6am .. I believe this has something to do with insulin and leptin secretion, but how and why ??? Perhaps cortisol rising at the wrong time and stimulating hunger ??
I generally fall asleep around 10pm or so, wake up around 7am. I wake up frequently to pee but can usually fall back asleep within 15-30mins … otherwise I am up at those very early hours with such a ravenous hunger, deep in my chest more than my stomach, that forces me out of bed since I cannot go to sleep otherwise. Then I eat 100-300 cals of fat/protein, and almost always end up having nightmares. Strange!
You say do not eat late at night .. Do you just mean right before bed?
Thank you!
Jessica Jane,
We will be publishing some follow-ups to this post, yes. That ravenous hunger could be morning cortisol rising early alongside low levels of leptin, or it could a hypoglycemia-type scenario left over from inadequate food the day before (or too many carbs too close to bedtime). It’s hard to say for sure. Stay tuned for our next post and see if that helps you understand this any better. You didn’t give me any info on your training time/type, diet quality/timing/quantity, etc., so it’s nearly impossible to give you detailed, accurate feedback. As far as eating late at night, we mean to try to allow 3-5 hours between your last meal/snack and bedtime, with no food intake at all after that. Hope this helps.
Dallas
My ravenous, biting hunger used to happen to me when I was a little girl, maybe only 5 or 6 when I was a sugar junkie. I’m thinking it has something to do with slight hypoglycemia. When you first got me hooked on paleo, I was eating very plentiful and had my carbs at about 70-120g, but I experienced some serious drops in blood sugar following intense, hr-long “cardio kickbox” sessions (I was still hooked!) that would result in excrutiating migraines, visual auras, and one time my hands started to shake and then went numb. This actually happened to me again a few weeks ago before going on a bikeride, even though I had eaten a big, hearty meal of pork and veggies and olive oil maybe 2hrs before. My boyfriend ran into a grocery store and bought me hard-boiled eggs, banana, some dark chocolate. ;-) I ate what I could and felt better…
I do an alteration on Wendler 5/3/1 twice a week for about 40-50 minutes. Squat, hip thrust, chin-ups, rows. Gains are good and I’ve only stalled once (after my 21st..doh.) I might put in a little “met-con” or “fun exercises” at the end that don’t kill me, for 5-15mins. I try to walk or do light bicycling or yoga/stretching when I have the time throughout the week. My diet is all paleo, with the inclusion of very dark (90%) cocoa and unsweetened almond milk (is that still paleo??) I realized sweet potatoes make my stomach kind of hurt, so now I just stick to canned pumpkin or different squashes cooked really well in my steamer. I probably only eat 1200-1600 calories a day, but then again, I’m really not as active as I used to be, and I’m at about 117lbs now.
I feel like if I don’t eat before bed, I’ll be hungry, and then wake up even MORE hungry. I woke up twice last night wanting to eat. I had an egg and passed back out. Very aggravating. Just was wondering if you had any insight, but will be looking out for your next series. Thank you!
Jess
Great post guys, thanks!
I was wondering if you guys have a(many) reference(s) for this statement: “Creating excessive inflammation via over-exercising (or, as we prefer, under-recovering) can further disturb leptin and insulin signaling.”
I know that this wasn’t the point of the article but was wondering if you could point me to any good studies/articles that relate to this. I’m interested as a coach as well as a perpetual student! Thanks!
P.J.
P.J.,
Shoot me an email at dallas at whole9life dot com and I’ll send you the research that I’ve got on hand regarding overtraining and insulin/leptin signaling. There is, of course, tons that I’ve read but not saved to my archive, but I’ll give you what I’ve got. Thanks for your interest.
Dallas
Thank you for this post. I have been seeing stuff in paleo circles about leptin’s role in body fat and I appreciate the way the you broke down this hormone’s role and effects in an easy to understand way. I am looking forward to your follow-up posts on this topic.
The points you highlight about the involvement of pancreatic beta cells in leptin signaling are very interesting to me. As a person with Type 1 diabetes (and no beta cells) I wonder if my leptin pathway is all screwed up.
I love your blog and appreciate the work that you do – keep it up!